RESCUE CCTA represents a potentially disruptive technology in terms of its impact on the clinical evaluation and management of coronary artery disease (CAD). This was highlighted by its inclusion in the Consensus Report on Initial National Priorities for Comparative Effectiveness Research (CER) issued by the Institute of Medicine (IOM). Specifically, the report recommends: "Compare the effectiveness of computed tomography (CT) angiography and conventional angiography in assessing coronary stenosis in patients at moderate pretest risk of coronary artery disease." An additional IOM aim stated in the Consensus Report, most likely in response to the results of the COURAGE trial, recommends research comparing the effectiveness of "aggressive medical management and percutaneous coronary interventions in treating stable coronary disease for patients of different ages and with different comorbidities." The results of the COURAGE trial suggest that patients with stable angina diagnosed with CAD and initially treated with optimal medical therapy (OMT) alone have no difference in outcomes in comparison to individuals treated with both OMT and percutaneous coronary intervention (PCI). CCTA, by explicitly identifying patients with potentially significant left main disease, can safely select patients for OMT without requiring invasive coronary angiography. This is not the case for the more traditional single photon emission tomography myocardial perfusion imaging (SPECT MPI) where patients with a positive test for CAD will require invasive angiography to identify potential left main disease prior to the safe initiation of OMT. We propose the Randomized Evaluation of Patients with Stable Angina Comparing Utilization of Noninvasive Examinations (RESCUE), a multi-center randomized, controlled trial. This study builds on the results of the COURAGE trial by comparing CCTA and SPECT-MPI integrated into a care paradigm featuring initial treatment with optimized medical therapy for patients diagnosed with CAD without significant disease in the left main coronary artery. Patients will be followed for a composite endpoint of major adverse cardiac events (MACE) and cross-over to revascularization over a 12-24 month period. Several comparative effectiveness analyses will be performed. We hypothesize that the CCTA arm will be associated with no increase in major coronary events (MACE) or revascularization, decreased cost and increased cost-effectiveness in comparison to SPECT-MPI. Findings are expected to result in validation of an evolving new standard of care for patients with stable angina that takes advantage of CCTA to more cost effectively drive appropriate care. PUBLIC HEALTH RELEVANCE: RESCUE is a multi-center randomized, controlled trial comparing coronary CT angiography (CCTA) and single photon emission tomography myocardial perfusion imaging (SPECT-MPI) integrated into a stable angina care paradigm featuring optimized medical therapy for patients diagnosed with CAD without significant disease in the left main coronary artery. Patients will be followed for a composite endpoint of major adverse cardiac events (MACE) and cross-over to revascularization over a 12-24 month period. Several comparative effectiveness analyses will be performed. The investigators hypothesize that the CCTA arm will be associated with no increase in major coronary events (MACE) or revascularization, decreased cost and increased cost-effectiveness in comparison to SPECT-MPI. Findings are expected to result in validation of an evolving new standard of care for patients with stable angina that takes advantage of CCTA to more cost effectively drive appropriate care.